Month: September 2022

Saha, Achinto;Zhao, Shengyuan;Chen, Zhao;Georgiou, George;Stone, Everett;Kidane, Dawit;DiGiovanni, John published 《Combinatorial Approaches to Enhance DNA Damage following Enzyme-Mediated Depletion of L-Cys for Treatment of Pancreatic Cancer》 in 2021. The article was appeared in 《Molecular Therapy》. They have made some progress in their research.Reference of ((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold The article mentions the following:

Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest forms of cancer with very few available therapeutic options. We previously reported that an engineered human enzyme, cyst(e)inase, which degrades L-cysteine (L-Cys) and cystine, inhibits growth of multiple cancer cells, including PDAC both in vitro and in vivo. Here, we show that cyst(e)inase treatment leads to increased clustered oxidative DNA damage, DNA single-strand breaks, apurinic/apyrimidinic sites, and DNA double-strand breaks (DSBs) in PDAC cells sensitive to intracellular depletion of L-Cys that is associated with reduced survival. BRCA2-deficient PDAC cells exhibited increased DSBs and enhanced sensitivity to cyst(e)inase. The blocking of a second antioxidant pathway (thioredoxin/thioredoxin reductase) using auranofin or inhibiting DNA repair using the poly (ADP-ribose) polymerase (PARP) inhibitor, olaparib, led to significant increases in DSBs following cyst(e)inase treatment in all PDAC cells examined Cyst(e)inase plus olaparib also synergistically inhibited growth of sensitive and resistant PDAC cells in both xenograft and allograft tumor models. Collectively, these results demonstrate an important role for oxidative DNA damage and ultimately DNA DSBs in the anticancer action of cyst(e)inase. The data further show the potential for combining agents that target alternate antioxidant pathways or by targeting DNA repair pathways or genetic liabilities in DNA repair pathways to enhance the therapeutic action of cyst(e)inase for PDAC. The experimental procedure involved many compounds, such as ((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold (cas: 34031-32-8) .

((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold(cas: 34031-32-8) is a disease-modifying antirheumatic drug (DMARD) and has been used to study the anti-proliferative effects against OVCAR-3 human ovarian carcinoma cells.Reference of ((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold

Reference:
Phosphine ligand,
Chiral phosphines in nucleophilic organocatalysis

Wang, Guosong;Chen, Ruiqi;Huang, Pengfei;Hong, Junping;Cao, Jiali;Wu, Qian;Zheng, Wei;Lin, Lina;Han, Qiangyuan;Chen, Yixin;Xia, Ningshao published 《Adefovir dipivoxil efficiently inhibits the proliferation of pseudorabies virus in vitro and in vivo》. The research results were published in《Antiviral Research》 in 2021.Synthetic Route of C20H36AuO9PS The article conveys some information:

Since 2011, highly pathogenic pseudorabies virus (PRV) variants that emerged on many farms in China have posed major economic burdens to the animal industry and have even recently caused several human cases of viral encephalitis. Currently, there are no approved effective drugs to treat PRV associated diseases in humans or pigs. Thus, it is important to develop a new effective drug for the treatment of PRV infection. To this end, we established a novel rapid method to screen drugs against PRV from 1818 kinds of small mol. drugs approved by the FDA. Using this method, we identified 21 kinds of them that can strongly suppress the proliferation of PRV. Mitoxantrone, puromycin dihydrochloride, mitoxantrone hydrochloride and adefovir dipivoxil effectively inhibited PRV in vitro. Of them, only adefovir dipivoxil could potently protect mice against lethal PRV infection. Our work identifies several kinds of potential therapeutics against PRV and may offer important guidance for controlling PRV epidemics and treating associated diseases in humans and animals. And ((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold (cas: 34031-32-8) was used in the research process.

((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold(cas: 34031-32-8) is a gold(I)-phosphine thiolate small molecule described to produce antiinflammatory and antiarthritic effects.Synthetic Route of C20H36AuO9PS

Reference:
Phosphine ligand,
Chiral phosphines in nucleophilic organocatalysis

Miyamoto, Yukiko;Aggarwal, Shubhangi;Celaje, Jeff Joseph A.;Ihara, Sozaburo;Ang, Jonathan;Eremin, Dmitry B.;Land, Kirkwood M.;Wrischnik, Lisa A.;Zhang, Liangfang;Fokin, Valery V.;Eckmann, Lars published 《Gold(I) Phosphine Derivatives with Improved Selectivity as Topically Active Drug Leads to Overcome 5-Nitroheterocyclic Drug Resistance in Trichomonas vaginalis》 in 2021. The article was appeared in 《Journal of Medicinal Chemistry》. They have made some progress in their research.Electric Literature of C20H36AuO9PS The article mentions the following:

Trichomonas vaginalis causes the most common, nonviral sexually transmitted infection. Only metronidazole (Mz) and tinidazole are approved for treating trichomoniasis, yet resistance is a clin. problem. The gold(I) complex, auranofin, is active against T. vaginalis and other protozoa but has significant human toxicity. In a systematic structure-activity exploration, authors show here that diversification of gold(I) complexes, particularly as halides with simple C1-C3 trialkyl phosphines or as bistrialkyl phosphine complexes, can markedly improve potency against T. vaginalis and selectivity over human cells compared to that of the existing antirheumatic gold(I) drugs. All gold(I) complexes inhibited the two most abundant isoforms of the presumed target enzyme, thioredoxin reductase, but a subset of compounds were markedly more active against live T. vaginalis than the enzyme, suggesting that alternative targets exist. Furthermore, all tested gold(I) complexes acted independently of Mz and were able to overcome Mz resistance, making them candidates for the treatment of Mz-refractory trichomoniasis. And ((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold (cas: 34031-32-8) was used in the research process.

((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold(cas: 34031-32-8) is a gold(I)-phosphine thiolate small molecule described to produce antiinflammatory and antiarthritic effects.Electric Literature of C20H36AuO9PS

Reference:
Phosphine ligand,
Chiral phosphines in nucleophilic organocatalysis

Yamashita, Masamichi published 《Auranofin: Past to Present, and repurposing》. The research results were published in《International Immunopharmacology》 in 2021.Safety of ((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold The article conveys some information:

Auranofin (AF), a gold compound, has been used to treat rheumatoid arthritis (RA) for more than 40 years; however, its mechanism of action remains unknown. We revealed that AF inhibited the induction of proinflammatory proteins and their mRNAs by the inflammatory stimulants, cyclooxygenase-2 and inducible nitric oxide synthase, and their upstream regulator, NF-κB. AF also activated the proteins peroxyredoxin-1, Kelch-like ECH-associated protein 1, and NF-E2-related factor 2, and inhibited thioredoxin reductase, all of which are involved in oxidative or electrophilic stress under physiol. conditions. Although the cell membrane was previously considered to be permeable to AF because of its hydrophobicity, the mechanisms responsible for transporting AF into and out of cells as well as its effects on the uptake and excretion of other drugs have not yet been elucidated. Antibodies for cytokines have recently been employed in the treatment of RA, which has had an impact on the use of AF. Trials to repurpose AF as a risk-controlled agent to treat cancers or infectious diseases, including severe acute respiratory syndrome coronavirus 2/coronavirus disease 2019, are ongoing. Novel gold compounds are also under development as anti-cancer and anti-infection agents.((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold (cas: 34031-32-8) were involved in the experimental procedure.

((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold(cas: 34031-32-8) is an efficient inducer of mitochondrial membrane permeability transition pore in the presence of calcium ions related to its inhibition of mitochondrial thioredoxin reductase.Safety of ((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold

Reference:
Phosphine ligand,
Chiral phosphines in nucleophilic organocatalysis

Lamarche, J.;Bierla, K.;Ouerdane, L.;Szpunar, J.;Ronga, L.;Lobinski, R. published 《Mass spectrometry insights into interactions of selenoprotein P with auranofin and cisplatin》 in 2022. The article was appeared in 《Journal of Analytical Atomic Spectrometry》. They have made some progress in their research.Formula: C20H36AuO9PS The article mentions the following:

The reactivity of selenoprotein P (a serum selenoprotein containing 10 selenocysteine (SeCys), 17 cysteine (Cys) and 14 histidine (His) residues) with two metallodrugs (auranofin and cisplatin) was investigated. The selenoprotein was purified from human serum by sequential affinity chromatog. using immobilized metal (Co2+) affinity chromatog. (IMAC) and heparine affinity, followed by solid-phase extraction preconcentration The purified selenoprotein P was sequenced by nanoLC-MS/MS to reach a complete sequence coverage. It eluted from SEC as two major peaks likely to correspond to the glycosylated and non-glycosylated forms and a minor one, probably a truncated form. Size-exclusion chromatog. with the selective Se (78Se) and metal (197Au or 195Pt) detection by ICP MS showed the co-elution of selenoprotein P forms with Au and with Pt. SEC-ICP MS of the tryptic digest showed a considerable shift of the elution of selenium towards the lower mol. masses while preserving the co-elution of selenium and the metal at some elution times. NanoHPLC – electrospray MS/MS anal. of the post-reaction mixture demonstrated the formation of peptides with the privileged binding to Cys and His residues for cisplatin and SeCys and Cys residues for auranofin. And ((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold (cas: 34031-32-8) was used in the research process.

((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold(cas: 34031-32-8) is a potent inhibitor of selenoenzyme thioredoxin reductase (TrxR), which is involved in defense against oxidative stress.Formula: C20H36AuO9PS

Reference:
Phosphine ligand,
Chiral phosphines in nucleophilic organocatalysis

Rimkus, Audrius;Sewald, Norbert published 《First Synthesis of a β²-Homoamino Acid by Enantioselective Catalysis》. The research results were published in《Organic Letters》 in 2003.Formula: C38H34NO2P The article conveys some information:

The enantioselective conjugate addition of diethylzinc to the activated nitroolefin Me 3-nitropropenoate is efficiently catalyzed by copper(I) complexes with BINOL-based enantiopure phosphoramidite ligands. The nitroolefin moiety acts as the predominant Michael acceptor, giving rise to the unambiguous formation of Me 2-ethyl-3-nitropropanoate. Moderate to excellent enantioselectivities and high chem. yields are obtained. The product can easily be transformed into a β²-homoamino acid, 2-[(tert-butoxycarbonyl)aminomethyl]butanoic acid. And (11bS)-2,6-Dimethyl-N,N-bis(1-phenylethyl)dinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepin-4-amine (cas: 201732-49-2) was used in the research process.

(11bS)-2,6-Dimethyl-N,N-bis(1-phenylethyl)dinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepin-4-amine(cas: 201732-49-2) is a compound of chiral-phosphine-ligands. At present, the synthesis of new chiral phosphines designed specifically for nucleophilic organocatalysis remains a significant challenge.Formula: C38H34NO2P

Reference:
Phosphine ligand,
Chiral phosphines in nucleophilic organocatalysis

Proetto, Maria T.;Alexander, Kelsey;Melaimi, Mohand;Bertrand, Guy;Gianneschi, Nathan C. published 《Cyclic (Alkyl)(Amino)Carbene (CAAC) Gold(I) Complexes as Chemotherapeutic Agents》 in 2021. The article was appeared in 《Chemistry – A European Journal》. They have made some progress in their research.Safety of ((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold The article mentions the following:

Cyclic (Alkyl)(Amino)Carbenes (CAACs) have become forceful ligands for gold due to their ability to form very strong ligand-metal bonds. Inspired by the success of Auranofin and other gold complexes as antitumor agents, we have studied the cytotoxicity of bis- and mono-CAAC-gold complexes on different cancer cell lines: HeLa (cervical cancer), A549 (lung cancer), HT1080 (fibrosarcoma) and Caov-3 (ovarian cancer). Further investigations aimed at elucidating their mechanism of action are described. This includes quantification of affinities for TrxR, evaluation of their bioavailability and determination of associated cell death process. Moreover, Transmission Electron Microscopy (TEM) was used to study morphol. changes upon exposure. Noticeably, a significant reduction in non-specific binding to serum proteins was observed with CAAC complexes when compared to Auranofin. These results confirm the potential of CAAC-gold complexes in biol. environments, which may result in more specific drug-target interactions and decreased side effects. To complete the study, the researchers used ((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold (cas: 34031-32-8) .

((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold(cas: 34031-32-8) is a disease-modifying antirheumatic drug (DMARD) and has been used to study the anti-proliferative effects against OVCAR-3 human ovarian carcinoma cells.Safety of ((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold

Reference:
Phosphine ligand,
Chiral phosphines in nucleophilic organocatalysis

Meng, Fanke;Haeffner, Fredrik;Hoveyda, Amir H. published 《Diastereo- and enantioselective reactions of bis(pinacolato)diboron, 1,3-enynes, and aldehydes catalyzed by an easily accessible bisphosphine-Cu complex》 in 2014. The article was appeared in 《Journal of the American Chemical Society》. They have made some progress in their research.Reference of (R)-2,2′-Bis[bis(3,5-trifluoromethylphenyl)phosphino]-4,4′,6,6′-tetramethoxy)-1,1′-biphenyl The article mentions the following:

Catalytic enantioselective multicomponent processes involving bis(pinacolato)diboron B₂(pin)₂, 1,3-enynes RCCCH:CH₂ (R = Ph, aryl, 3-thienyl, 1-cyclohexenyl, TIPSOCMe₂, Et₃Si), and aldehydes R¹CHO (R¹ = aryl, 3-benzo[b]thienyl, cinnamyl, cyclohexenyl, PhCH₂CH₂) resulting in chiral bis(homopropargyl) diols R¹CH(OH)CH(CH₂OH)CCR are disclosed; the resulting compounds contain a primary C-B(pin) bond, as well as alkyne- and hydroxyl-substituted tertiary carbon stereogenic centers. A critical feature is the initial enantioselective Cu-B(pin) addition to an alkyne-substituted terminal alkene. This and other key mechanistic issues have been investigated by DFT calculations Reactions are promoted by the Cu complex of a com. available enantiomerically pure bis-phosphine and are complete in 8 h at ambient temperature; products are generated in 66-94% yield (after oxidation or catalytic cross-coupling), 90:10 to >98:2 diastereomeric ratio, and 85:15-99:1 enantiomeric ratio. Aryl-, heteroaryl-, alkenyl-, and alkyl-substituted aldehydes and enynes can be used. Utility is illustrated through catalytic alkylation and arylation of the organoboron products as well as applications to synthesis of fragments of tylonolide and mycinolide IV.(R)-2,2′-Bis[bis(3,5-trifluoromethylphenyl)phosphino]-4,4′,6,6′-tetramethoxy)-1,1′-biphenyl (cas: 1365531-84-5) were involved in the experimental procedure.

(R)-2,2′-Bis[bis(3,5-trifluoromethylphenyl)phosphino]-4,4′,6,6′-tetramethoxy)-1,1′-biphenyl(cas: 1365531-84-5) is a compound of chiral-phosphine-ligands. At present, the synthesis of new chiral phosphines designed specifically for nucleophilic organocatalysis remains a significant challenge.Reference of (R)-2,2′-Bis[bis(3,5-trifluoromethylphenyl)phosphino]-4,4′,6,6′-tetramethoxy)-1,1′-biphenyl

Reference:
Phosphine ligand,
Chiral phosphines in nucleophilic organocatalysis

Massai, Lara;Cirri, Damiano;Marzo, Tiziano;Messori, Luigi published 《Auranofin and its analogs as prospective agents for the treatment of colorectal cancer》. The research results were published in《Cancer Drug Resistance》 in 2022.Application of 34031-32-8 The article conveys some information:

A review. Today colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. This disease is poorly chemo-sensitive toward the existing medical treatments so that new and more effective therapeutic agents are urgently needed and intensely sought. Platinum drugs, oxaliplatin in particular, were reported to produce some significant benefit in CRC treatment, triggering the general interest of medicinal chemists and oncologists for metal-based compounds as candidate anti-CRC drugs. Within this frame, gold compounds and, specifically, the established antiarthritic drug auranofin with its analogs, form a novel group of promising anticancer agents. Owing to its innovative mechanism of action and its favorable pharmacol. profile, auranofin together with its derivatives are proposed here as novel exptl. agents for CRC treatment, capable of overcoming resistance to platinum drugs. Some encouraging results in this direction have already been obtained. A few recent studies demonstrate that the action of auranofin may be further potentiated through the preparation of suitable pharmaceutical formulations capable of protecting the gold pharmacophore from unselective reactivity or through the design of highly synergic drug combinations. The perspectives of the research in this field are outlined. The experimental procedure involved many compounds, such as ((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold (cas: 34031-32-8) .

((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold(cas: 34031-32-8) is a gold(I)-phosphine thiolate small molecule described to produce antiinflammatory and antiarthritic effects.Application of 34031-32-8

Reference:
Phosphine ligand,
Chiral phosphines in nucleophilic organocatalysis